INTRAVENOUS GLUTATHIONE AS A ‘SKIN WHITENING’ AGENT
Evidence of IV Glutathione’s Efficacy as a skin whitener: Insufficient
Despite the numerous anecdotal reports and testimonials of dramatic skin whitening after IV glutathione, there is still no sufficient scientific evidence to show that IV glutathione can significantlylighten the skin based on a local pilot study. There has been no evidence generated regarding the degree of lightening that can be achieved nor the duration of the lightening effect.
One before-and –after, open label clinical trial investigated the efficacy of 600 mg IV glutathione once weekly for 10 consecutive weeks on 22 healthy female volunteers. Only 8 of the 21 evaluable subjects had measurable reduction in melanin indices (using a Mexameteron a non-sun exposed site) after the treatment period while only 5 subjects observed skin lightening and also had reductions in melanin indices1.
Safety profile of IV glutathione IV glutathione is a drug and not merely a nutritional supplement. In the Philippines, IV glutathione has been associated with adverse events, as reported in local studies and by fellow dermatologists, medical colleagues, and patients themselves. These adverse events range from mild, transient symptoms like headache and skin eruptionsto severe drug reactions requiring hospitalization2. These injections have also caused pain, inflammation, or pruritus at the puncture sites especially when the drug extravasates during the injection1. Patient co-morbidities, the high concentration, high doses, and rapid infusion rates of glutathione administration may be factors influencing the occurrence of adverse events. Additives, contaminants, and fake glutathione products are also possible causes of adverse reactions.
One Philippine clinical trial documented three (3) adverse events occurring after the second or third dose of IV glutathione: one case of mild chest discomfort followed by transient headache; two cases of myalgia and ‘tired feeling’ for two days after injections1.
One cross-sectional survey with twenty five (25)Filipino dermatologist respondents reported seven (7) adverse events among five (5) patients. Those who received IV glutathione reportedly had dizziness, cutaneous eruptions (morbilliform, urticaria and angioedema), erratic blood sugar in a diabetic, chills, and headache. One patient who took oral glutathione supplements developed pityriasisrosea-like eruptions2.
One Philippine cross-sectional study examined thirty six (36) apparently healthy Filipinos taking glutathione oral supplements or IV glutathione for cosmetic purposes. Investigators were able to detect subclinical hyperthyroidism in two (2) cases (5.5%) and solid or cystic thyroid nodules in twenty(20) participants. Adverse events reported were increased appetite, weight gain or loss, insomnia, heat intolerance, flatulence, polyuria, easy fatigability, headache, palpitations, thirst, dizziness, and easy bruisability3.
The Uppsala Monitoring Centre, an independent foundation and a centre for international service and scientific research, has compiled thirty two (32) reports of adverse events associated with IV glutathione and twenty three (23) reports associated with non-IV glutathione products. Most reports emanated from Japan and Italy4.
ADVISORY FOR PDS MEMBERS REGARDING IV GLUTATHIONE USE
Food and Drug Administration Warning to the Public (May 12, 2011)
“The use of glutathione IV as a skin whitener is not approved by the FDA. The public is strongly warned to refrain from using glutathione for this purpose in light of potential harm associated with its use.”
Members of the PDS are advised to heed the warning of the FDA.
1. There is a legal issue on the use of IV glutathione products. For the past years, IV glutathione products have been distributed and used in the Philippines even without FDA approval. Prescribing or administering unlicensed drugs isconsidered illegal. Injections or IV infusions administered by non-physicians without the order of a physician is also considered illegal. In 2011, only one IV glutathione product was granted a license by FDA. It has only been approved as a supplement to help prevent neuropathy induced by cisplatin or oxaliplatin chemotherapy, yet this product is being promoted for skin whitening or rejuvenation.
2. The second issue is on patient safety. The quality and safety of unlicensed drugs cannot be assured. The risk of adverse events increases due to fake, adulterated, or contaminated glutathione products. We also have to warn the public that the risk of harmful effects increases when non-physicians inject glutathione.
3. The third issue is on proper patient information regarding treatment options. Patients should be informed that IV glutathione is NOT a standard drug for lightening the skin and is currently undergoing scientific investigations regarding its effect on skin pigmentation. Patients should be properly informed about the standard treatment options, the licensed products for skin whitening, and that basic sun protection measures and sun avoidance also lead to skin lightening.
4. Off-label use of IV glutathione: Dermatologists do have leeway to prescribe or use certain drugs for medical indications other than the FDA-approved uses (i.e.off-label use). However, the physician should have the informed consent of the patient before using IV glutathione as an off-label skin whitener.
The physician should clearly inform the patient that the IV glutathione and similar drugs are NOT standard treatments for skin whitening. The physician should also inform the patient that its efficacy and safety have yet to be established. The patient has to be informed about the documented adverse effects of IV glutathione such as headache, dizziness, chest heaviness, or myalgias.
IV Glutathione is a good drug. IV Glutathione was originally and primarily intended for supportive therapy of sick people. Glutathione supplementation has been found to be useful for patients who are ‘glutathione-depleted’ due to chronic or severe illness5. However, the rampant use of IV glutathione as a skin whitener has made the public believe that glutathione products are primarily for skin whitening. We should be exploring IV glutathione’s uses mainly for medical rather than cosmetic purposes.
REFERENCES
1. Katipunan, Kathleen Kwan and Lillian Villafuerte, Intravenous Glutathione as a depigmenting agent: A pilot study on its efficacy and safety. Department of Dermatology, Jose R. Reyes Memorial Medical Center, Manila, Philippines, 2009 (In press)
2. Eleonor B. Asuncion and Belen LDofitas.Adverse Effects observed by Filipino Dermatologists among Patients using Glutathione-containing Products: An Exploratory Study. Dept. of Dermatology, St. Luke’s Medical Center, 2010. (Unpublished)
3. Danivic J.N. Ramirez, Jade C. Vergara-Villaluz, Maria PilarLagdameo-Leuenberger, Gabriel V. Jasul, Jr., Joselynna S. Añel-Quimpo. Prevalence of Thyroid Dysfunction Among Individuals Taking Glutathione Supplementation: A Cross-Sectional Study PreliminaryReport
4. The UPPSALA Monitoring report (as of May 2011)
5. Alolod, Maria Kristina, Alonte, Angelica Joy, Dofitas, Belen. Effects of Glutathione Supplementation: A Systematic Review and Meta-Analysis. St. Luke’s Medical Center, Department of Internal Medicine, 2008 (Unpublished).
Other References
1. Paolisso G et. al. 1992. Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin-dependent diabetics. Am J Physiol. 263:435-40.
2. Cascinu S, Cordella L, Del Ferro E, Fronzoni M, Catalano G. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. J ClinOncol. 1995 Jan;13(1): 26-32.
3. Smyth, C et al, Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: Results of a double blind, randomised trial. Annals of Oncology 8: 569-573, 1997
4. Kugiyama,K et al, Intracoronary Infusion of Reduced Glutathione Improves Endothelial Vasomotor Response to Acetylcholine in Human Coronary Circulation. Circulation 1998; 97; 2299-2301
5. De Mattia G et al, Influence of Reduced Glutathione Infusion on Glucose Metabolism in Patients with Non-Insulin-Dependent Diabetes Mellitus. Metabolism, Vo147, No 8 (August), 1998: pp 993-997 993
6. G.F. Bagnatoet. al. 1999. Effect of Inhaled Glutathione on Airway Response to ‘Fog’ Challenge in Asthmatic Patients. Respiration; 66:518–521.
7. Ortolani, O et al. 2000. The Effect of Glutathione and N-Acetylcysteine on Lipoperoxidative Damage in Patients with Early Septic Shock. Am J RespirCrit Care Med Vol 161. pp 1907– 1911
8. Arosio, E et al, Effect of Glutathione Infusion on Leg Arterial Circulation, Cutaneous Microcirculation, and Pain-Free Walking Distance in Patients With Peripheral Obstructive Arterial Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. Mayo Clin Proc. 2002;77:754-759
9. Cascinu S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli AM, Beretta GD, Ubiali E, Catalano G. Neuroprotective effect of reduced glutathione on oxiplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J ClinOncol. 2002 Aug 15;20(16):3478-3483
10. Valencia, E. et. al. 2002. Practicalities of Glutathione supplementation in nutritional support. CurrOpinClinNutrMetab Care. 5:321±326
11. Arosio, E et al, Effect of Glutathione Infusion on Leg Arterial Circulation, Cutaneous Microcirculation, and Pain-Free Walking Distance in Patients With Peripheral Obstructive Arterial Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. Mayo Clin Proc. 2002;77:754-759
12. Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother. 2003 May-Jun; 57(3-4); 145-155
13. Wu, G et al, Glutathione Metabolism and Its Implications for Health. J. Nutr. 134: 489–492, 2004
14. Villarama, CD &Maibach HI. Glutathione as a depigmenting agent: an overview. Int. J CosmetSci 2005 June; 27 (3): 147-153.
15. Enomoto, M et al, Combination glutathione and anthocyanins as an alternative for skincare during external-beam radiation. Am J of Surgery 189 (2005) 627–631
16. Bishop, C et al,. A Pilot Study of the Effect of Inhaled Buffered Reduced Glutathione on the Clinical Status of Patients With Cystic Fibrosis. Chest 2005;127;308-317
17. Dofitas BL. Glutathione supplements and the skin. Oral Presentation. UPPGH Postgraduate Course ‘Women’s Dermatology’ March 2008
18. Ramirez DJN, Vergara-Villaluz JC, Lagdameo-Leunberger MP, Jasul GV Jr, Anel-Quimpo JS. Prevalence of thyroid dysfunction among individuals taking glutathione supplementation: a cross-sectional study preliminary report. Phil J Intern Med. 2010;48(3):1-6
Prepared By:
BELEN LARDIZABAL-DOFITAS,, MD, FPDS
For the Board of Directors:
(original signed)
MA. TERESITA G. GABRIEL, MD, FPDS
PDS President
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The Philippine Dermatological Society in its desire to help the public distinguish legitimate, board certified dermatologists from fake pseudodermatologists, conceptualized the making of a sign or symbol that PDS members can easily display or use in their respective clinics. The "Seal of Excellence" was thus finally made public last .. 
Locate the nearest Accredited Dermatologist in your area. 
To advocate public safety on skin health through information dissemination and consultation with competent and certified PDS Dermatologist 
Dear Colleagues,
